PARPs in lipid metabolism and related diseases. (November 2021)

• Record Type: Journal Article
• Authors: Szántó, Magdolna; Gupte, Rebecca; Kraus, W. Lee; Pacher, Pal; Bai, Peter
• Is Part Of: Progress in lipid research. Volume 84(2021)
• Publication Date: 2021-11
• Subjects: PARP -- ARTD -- cholesterol -- triglyceride -- polyunsaturated fatty acid -- HDL -- LDL -- SREBP -- ACAT1 -- ABCA1 -- lipophagy -- PGC1α -- nuclear receptor -- lipotoxicity -- atherosclerosis -- PPARα -- PPARγ -- Estrogen receptor -- C/EBP; ABCA1 ATP-binding cassette sub-family A Member 1 -- ACAT1 Mitochondrial acyl-coenzyme A/cholesterol acyltransferase-1 -- ACBD3 Acyl-CoA-binding domain containing 3 -- ADPR ADP-ribose -- AFLD Alcoholic fatty liver disease -- AHR Aryl hydrocarbon receptor -- ALDH2 Aldehyde dehydrogenase 2 -- AMPK AMP-activated protein kinase -- ApoB Apolipoprotein B -- AR Androgen receptor -- ARH3 ADP-ribosyl-acceptor hydrolase-3 -- ARTs ADP-ribosyl transferases -- ARTD Diphtheria toxin-like ADP-Ribosyltransferases -- C/EBPα CCAAT-enhancer-binding protein alpha -- cyp Cytochrome P450 -- DGAT Diacylglycerol O-acyltransferase -- DHT dihydrotestosterone -- EBF Early B cell factor -- EMA European Medicines Authority -- eNOS Endothelial nitrogen oxide synthase -- EPHX1 Microsomal epoxide hydrolase -- ERα Estrogen receptor alpha -- ERK Extracellular signal-regulated kinase -- FABP7 Fatty acid binding protein 7 -- FDA Food and Drug Administration -- FoxO1 Forkhead transcription factor O1 -- GATA GATA-binding factor -- GLP-1 Glucagon-like peptide-1 -- Glut4 Glucose transporter-4 -- GR Glucocorticoid receptor -- hADMSC Human adipose tissue-derived mesenchymal stem cells -- HCD High cholesterol diet -- HDAC Histone deacetylase -- HDL High density lipoprotein -- HFD High-fat diet -- HFRD High fructose diet -- HNF4 Hepatocyte nuclear factor 4 -- HPF1 Histone PARylation factor 1 -- Hsd17b11 Estradiol 17-beta-dehydrogenase 11 -- H2BE35 Histone H2B on glutamate 35 -- IDL Intermediate density lipoprotein -- IGF-1 Insulin-like growth factor-1 -- iNOS Inducible nitrogen oxide synthase -- InsR Insulin receptor -- iPSCs Induced pluripotent stem cells -- IRF Interferon-regulatory factor -- JNK Jun kinase -- KLF Krüppel-like factor -- LDL Low density lipoprotein -- LPS Bacterial lipopolysaccharide -- LXR Liver X receptor -- MARylation Mono(ADP-ribosyl)ation -- MCD Methionine-choline deficient -- mTORC1/2 Mammalian/mechanistic Target of Rapamycin Complex 1/2 -- NAD+ Oxidized nicotinamide adenine dinucleotide -- NAFLD Non-alcoholic fatty liver disease -- NASH Non-alcoholic steatohepatitis -- NCoR-1 Nuclear Receptor Corepressor 1 -- NEFA Non-esterified fatty acids -- NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells -- NMN Nicotinamide mononucleotide -- HIF hypoxia inducible factor -- NMNAT Nicotinamide/nicotinic acid mononucleotide adenylyltransferase -- NOR1 Neuron-derived orphan receptor 1 -- NOx Nitrogen oxides -- NR Nuclear receptor -- oxLDL Oxidized LDL -- OXPHOS Oxidative phosphorylation -- PAR poly(ADP-ribose) -- PARG Poly(ADP-ribose) glycohydrolase -- PARPi PARP inhibitor -- PARylation Poly(ADP-ribosyl)ation -- PPARα Peroxisome proliferator-activated receptor alpha -- PPARγ Peroxisome proliferator-activated receptor gamma -- PR Progesterone receptor -- P-Sel P-selectin -- PTMs Post-translational modifications -- RXRα Retinoid X-receptor alpha -- SAHA Suberoylanilide hydroxamic acid -- snoRNAs Short nucleolar RNAs -- SNP Single nucleotide polymorphism -- Srd5a1 5α-reductase -- SREBP Sterol regulatory-element binding protein -- StAR steroidogenic acute regulatory protein -- STAT Signal transducer and activator of transcription -- TC Total cholesterol -- TCDD 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin -- TF Transcription factors -- TG Serum triglyceride -- TLR2 Toll-like receptor-2 -- TNFα Tumor necrosis factor α -- TNKS Tankyrase -- TRPM2 Transient receptor potential M2 -- UCP Uncoupling protein -- V-Cam Vascular cell adhesion molecule 1 (CD106) -- VLDL Very low density lipoprotein -- VPA Valproic acid -- WAT White adipose tissue -- WHO World Health Organization -- 7KC 7-ketocholesterol -- 15-HC 15a-hydroxicholestene; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2021.101117
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: PARPs and tankyrases (TNKS) represent a family of 17 proteins. PARPs and tankyrases were originally identified as DNA repair factors, nevertheless, recent advances have shed light on their role in lipid metabolism. To date, PARP1, PARP2, PARP3, tankyrases, PARP9, PARP10, PARP14 were reported to have multi-pronged connections to lipid metabolism. The activity of PARP enzymes is fine-tuned by a set of cholesterol-based compounds as oxidized cholesterol derivatives, steroid hormones or bile acids. In turn, PARPs modulate several key processes of lipid homeostasis (lipotoxicity, fatty acid and steroid biosynthesis, lipoprotein homeostasis, fatty acid oxidation, etc.). PARPs are also cofactors of lipid-responsive nuclear receptors and transcription factors through which PARPs regulate lipid metabolism and lipid homeostasis. PARP activation often represents a disruptive signal to (lipid) metabolism, and PARP-dependent changes to lipid metabolism have pathophysiological role in the development of hyperlipidemia, obesity, alcoholic and non-alcoholic fatty liver disease, type II diabetes and its complications, atherosclerosis, cardiovascular aging and skin pathologies, just to name a few. In this synopsis we will review the evidence supporting the beneficial effects of pharmacological PARP inhibitors in these diseases/pathologies and propose repurposing PARP inhibitors already available for the treatment of various malignancies. Highlights: The activity of PARP enzymes is regulated by lipid molecules. PARP enzymes are involved in the regulation of lipid sensor transcription factors such as nuclear receptors or SREBPs. PARP activation is involved in the development of multiple diseases. These diseases include hyperlipidemia, dyslipidemia, AFLD, NAFLD, atherosclerosis, obesity and type II diabetes.